Background
Early results of tetralogy of Fallot (TOF) surgical repair are excellent, but patients are at risk for long-term complications. The purpose of the study was to determine to what extent ultrasonic tissue indices can be helpful in assessing the degree of pulmonary regurgitation (PR).
Methods
Fifty adults (26 men, 24 women; mean age, 34.4 years) who had undergone TOF correction were studied.
Results
Compared with normal controls, patients had decreased tricuspid annular plane systolic excursion (20.66 vs 26.79 mm, P < .05). In patients with TOF, maximal strain was reduced in all right ventricular free wall and interventricular septal segments. In patients with previous palliative shunts, lower maximal strain for RV basal segment was observed compared with subjects with no palliative surgery (−18.22% vs −22.27%, P < .05). Maximal systolic and early diastolic strain and strain rate values were significantly higher in patients with PR widths ≥ 3 mm compared with patients with PR widths < 3 mm.
Conclusions
Adults after TOF repair have decreased regional deformation of the right ventricle and intraventricular septum. Prior palliative treatment reduces the indices of right ventricular regional deformation. PR severity can be described by the extent of right ventricular regional deformation.
Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease. Early results of TOF surgical repair are excellent, but the patients are at risk for long-term complications. Approximately 5% require late reoperation for residual abnormalities.
One of the most common is pulmonary regurgitation (PR) leading to right ventricular (RV) enlargement, reduced exercise capacity, arrhythmias, and sudden cardiac death. Both the severity of PR as well as RV function are difficult to assess.
The current gold standard for the evaluation of PR severity and RV performance is cardiac magnetic resonance imaging, but this method is still not widely available. We believe that echocardiography with its novel imaging techniques (strain [ϵ] and strain rate [SR]) can provide insight into RV regional myocardial function and can be potentially important in clinical decision making.
The purpose of this study was to determine to what extent ultrasonic tissue indices are helpful in the assessment of the degree of PR and RV regional function in adults after total correction of TOF.
Methods
Study Population
Fifty consecutive adults who had undergone total correction of TOF were studied. At the time of examination, all subjects were in sinus rhythm. All but one had complete right bundle branch block on electrocardiography. Patients with significant RV outflow tract obstructions, significant tricuspid regurgitation, or residual ventricular septal defects (VSDs) on standard echocardiographic examination were excluded. Other exclusion criteria for the study were (1) age > 55 years, (2) cardiac surgery <6 months before the study, (3) any other congenital abnormalities or systemic diseases, (4) pacemaker, (5) pregnancy, and (6) New York Heart Association function class IV. The echocardiographic data obtained in patients with TOF were compared with those of the control group of 29 healthy volunteers. The study was approved by the local ethics committee, and each patient gave written consent.
Standard Echocardiographic Studies
Transthoracic echocardiographic examinations and Doppler myocardial imaging were performed using commercially available equipment (Vivid 7; GE Vingmed Ultrasound AS, Horten, Norway) with matrix probe M3S equipped with tissue velocity imaging. RV end-diastolic diameter was measured from M-mode recordings with the cursor placed at the tip of the mitral valve leaflets in the parasternal long-axis view. The main pulmonary artery diameter and RV outflow tract systolic and diastolic dimensions were measured by two-dimensional echocardiography at the left parasternal short-axis view. To assess global RV function, tricuspid annular plane systolic excursion (TAPSE) was acquired using the conventional M-mode method from the lateral point of the tricuspid valve in a standard apical four-chamber view. In addition, RV end-diastolic and end-systolic areas were measured to calculate RV fractional area change from the same apical four-chamber view. The RV myocardial performance index (Tei index) was defined as the sum of isovolumetric contraction time and isovolumetric relaxation time divided by ejection time and was measured from RV inflow and outflow Doppler velocities. PR was assessed by its duration from continuous-wave Doppler (PR time) and by the color Doppler pulmonary regurgitant jet width (PR width).
SR Imaging and Postprocessing
Doppler myocardial imaging data were acquired from the RV free wall and intraventricular septum (IVS) in the four-chamber view and stored digitally in a cine loop format. All studies were performed at high frame rates (about 180 frames/sec), at a depth of 16 cm and the narrowest image sector angle possible (usually 15°). Systolic and diastolic myocardial velocities, maximal ϵ, and systolic and diastolic SR were analyzed offline using EchoPAC version 5.0.1 (GE Healthcare, Milwaukee, WI). The program allowed the region of interest throughout the myocardial wall to be tracked automatically. The data for apical, middle, and basal segments of the interventricular septum and RV free wall were averaged from three consecutive cardiac cycles. All values were compared with those obtained from healthy subjects in the control group.
Statistical Analysis
Results, unless stated otherwise, are presented as mean ± SD. The normal distribution of variables was checked using the Kolmogorov-Smirnov test. Comparisons of means of differences among groups were calculated using unpaired Student’s t tests, and linear Pearson’s correlation was used to compare regional SR and ϵ values with the degree of PR. In the multivariate regression analysis, the backward elimination method with t tests was used to select variables. A confidence level of P < .05 was considered statistically significant.
Interobserver and intraobserver (E.K.) reproducibility was assessed in 10 randomly chosen patients and calculated as percentage of error, derived as the absolute difference between two measurements divided by the mean from the observations.
Results
Clinical Data
Fifty adults (26 men, 24 women; mean age, 34.4 ± 9.9 years) who had undergone total repair of TOF were studied. Sixteen patients (32%) had previous palliative systemic-pulmonary shunt procedures. The mean age at complete repair was 12.3 ± 11.8 years. Late reoperations were performed in 30 patients. The demographic and clinical data of the group are presented in Table 1 . The mean N-terminal pro–brain natriuretic peptide (NT-proBNP) level measured in 27 patients was elevated at 217.8 ± 138 pg/mL (normal range, 0–125 pg/mL).
| Variable | Value |
|---|---|
| Age (y) | 34.4 ± 9.9 (18–52) |
| Men | 26 (52%) |
| Age at total correction (y) | 12.3 ± 11.8 (2–43) |
| Palliative treatment | 16 (32%) |
| Time from last surgery (y) | 11.8 ± 6.3 (2–30) |
| Reoperation | 30 (60%) |
| Pulmonary homograft | 29 (58%) |
| Supraventricular arrhythmias | 10 (20%) |
| Ventricular arrhythmias | 10 (20%) |
| No medications | 8 (16%) |
| Diuretics | 13 (26%) |
| β-blockers | 28 (56%) |
| Angiotensin-converting enzyme inhibitors | 6 (12%) |
| Antiarrhythmic drugs | 6 (12%) |
Echocardiographic Data
Standard echocardiographic parameters in patients after TOF repair compared with healthy subjects are presented in Table 2 . We found that patients with TOF had significantly higher RV end-diastolic and systolic RV outflow tract dimensions, PA diameters, and RV systolic and diastolic areas. With respect to controls, patients after TOF repair had decreased TAPSE. Other indices of RV global function (fractional area change and myocardial performance index) did not differ between patients and controls.
| Echocardiographic parameter | Patients with TOF | Controls | P |
|---|---|---|---|
| RVEDD (cm) | 3.5 ± 1.05 | 2.3 ± 0.42 | <.0001 |
| RVOT diastolic diameter (cm) | 4.5 ± 4.2 | 3.2 ± 0.38 | NS |
| RVOT systolic diameter (cm) | 3.4 ± 3.5 | 1.8 ± 0.39 | .026 |
| PA diameter (cm) | 2.4 ± 0.26 | 2.2 ± 0.26 | .03 |
| Maximal PA velocity (m/sec) | 1.9 ± 0.75 | 0.8 ± 0.12 | <.0001 |
| RV systolic area (cm 2 ) | 20.7 ± 6.4 | 11.9 ± 2.8 | <.0001 |
| RV diastolic area (cm 2 ) | 27.9 ± 7.4 | 16.6 ± 2.4 | <.0001 |
| RV ET (msec) | 337.5 ± 45.4 | 324.5 ± 38.5 | NS |
| IVS (cm) | 1.04 ± 0.2 | 0.9 ± 0.13 | NS |
| Ascending aorta (cm) | 3.6 ± 0.53 | 2.6 ± 0.32 | <.0001 |
| TAPSE (mm) | 20.66 ± 5.13 | 26.79 ± 2.82 | <.0001 |
| RV DT (msec) | 205.2 ± 73.2 | 214.6 ± 78 | NS |
| RV FAC | 0.26 ± 0.1 | 0.28 ± 0.1 | NS |
| RV MPI | 0.39 ± 0.26 | 0.31 ± 0.1 | NS |
Tissue Doppler Data
Fourteen percent of the analyzed RV segments and 7.55% of IVS segments were not interpretable and were excluded from the study.
Myocardial Velocities
In the patient group, myocardial peak systolic and diastolic velocities were significantly lower in all RV free wall segments (e.g., 6.47 vs 10.83 cm/sec for systolic, −6.29 vs −10.26 cm/sec for early diastolic, and −3.63 vs −8.44 cm/sec for late diastolic velocities in the basal RV segment; P < .0001 for all comparisons). The decrease in velocity was also observed for IVS segments.
ϵ and SR
For patients with TOF, maximal ϵ was reduced in all segments of the RV free wall and interventricular septum compared with normal subjects ( Table 3 ).
| Myocardial wall | Wall segment | Patients with TOF | Controls | P |
|---|---|---|---|---|
| RV free wall | ||||
| Basal | −20.92 ± 6.51% | −28.06 ± 7.5% | <.0001 | |
| Middle | −20.14 ± 5.99% | −29.86 ± 6.99% | <.0001 | |
| Apical | −18.42 ± 5.75% | −31.21 ± 7.6% | <.0001 | |
| IVS | ||||
| Basal | −18.47 ± 4.73% | −21.2 ± 4.65% | <.05 | |
| Middle | −16.73 ± 4.15% | −21.17 ± 3.44% | <.0001 | |
| Apical | −15.17 ± 5.37% | −23.03 ± 3.44% | <.0001 |
We also found a statistically significant difference in systolic and late diastolic SR between patients with TOF and control subjects in RV segments ( Table 4 ), whereas early diastolic SR values were similar in the middle and apical segments of the right ventricle. In all segments of the interventricular septum, lower systolic and early diastolic SR values were recorded ( Table 5 ).
| Segment | SR (sec −1 ) | Patients with TOF | Controls | P |
|---|---|---|---|---|
| Basal | ||||
| Systolic | −1.2 ± 0.41 | −1.43 ± 0.41 | <.01 | |
| Early diastolic | 1.93 ± 0.61 | 2.2 ± 1.2 | <.05 | |
| Late diastolic | 0.64 ± 0.48 | 1.2 ± 0.45 | <.0001 | |
| Middle | ||||
| Systolic | −1.05 ± 0.37 | −1.49 ± 0.42 | <.0001 | |
| Early diastolic | 1.92 ± 0.73 | 2.24 ± 0.8 | NS | |
| Late diastolic | 0.63 ± 0.46 | 1.32 ± 0.5 | <.0001 | |
| Apical | ||||
| Systolic | −1.0 ± 0.36 | −1.7 ± 0.55 | <.0001 | |
| Early diastolic | 2.1 ± 0.76 | 2.4 ± 0.98 | NS | |
| Late diastolic | 0.57 ± 0.49 | 1.42 ± 0.64 | <.0001 |
| Segment | SR (sec −1 ) | Patients with TOF | Controls | P |
|---|---|---|---|---|
| Basal | ||||
| Systolic | −0.92 ± 0.24 | −1.1 ± 0.27 | <.01 | |
| Early diastolic | 1.45 ± 0.58 | 1.73 ± 0.6 | <.05 | |
| Late diastolic | 0.9 ± 0.37 | 1.04 ± 0.37 | NS | |
| Middle | ||||
| Systolic | −0.94 ± 0.26 | −1.1 ± 0.29 | <.01 | |
| Early diastolic | 1.31 ± 0.48 | 1.71 ± 0.48 | <.001 | |
| Late diastolic | 0.81 ± 0.29 | 0.96 ± 0.33 | NS | |
| Apical | ||||
| Systolic | −0.81 ± 0.27 | −1.2 ± 0.25 | <.001 | |
| Early diastolic | 1.62 ± 0.69 | 2.29 ± 0.71 | <.001 | |
| Late diastolic | 0.85 ± 0.35 | 1.04 ± 0.39 | NS |
Of note was a significant correlation between TAPSE in patients with TOF and RV maximal ϵ value measured for the middle segment ( Figure 1 ). The higher TAPSE, the greater the local deformation in the middle RV segments. Also, a significant relationship between RV Tei index and systolic SR in the basal RV segment was observed ( r = 0.29, P < .05).
Patients with TOF were divided into those with ( n = 29) and without ( n = 21) pulmonary homografts implanted. In patients with pulmonary homografts, smaller PR jet widths were observed (3.82 vs 5.86 mm in patients without homografts), although the difference was not statistically significant ( P = .09). No differences in RV deformation data between patients with pulmonary homografts and the rest of the group were found. Neither did the residual VSDs (left-to-right shunt < 1.5:1) recorded in 14 subjects influence the RV regional myocardial function measured with ϵ and SR. However, in patients with previous palliative shunts ( n = 16) lower maximal ϵ values for the RV basal segment were observed compared with subjects with no palliative surgery (–18.22% vs −22.27%, respectively, P < .05). No differences in NT-proBNP levels between the subgroups of patients mentioned above were found. In the multivariate regression analysis, we analyzed the influence of clinical factors and echocardiographic parameters on RV deformation. We took into account age, palliative shunts, age at total repair, time from the last operation, pulmonary homograft implantation, RV dimensions, fractional area change, myocardial performance index, TAPSE, PR width, and PR duration. The analysis revealed a significant influence of palliative shunts and the time elapsed from the last surgery on the maximal ϵ values in the basal segments of the right ventricle.
PR
PR was detected in 42 of 50 patients (84%). The mean PR time was 434.8 ± 125.2 msec, and the mean PR width was 5.6 ± 4.07 mm (range, 1–18 mm). We found a significant correlation between PR width and early diastolic SR values for the middle RV ( Figure 2 ) and apical IVS segments ( r = 0.59, P < .05). The whole study group was divided according to the degree of PR. In patients with PR widths ≥ 3 mm ( n = 32), RV end-diastolic dimensions were larger compared with patients with PR widths of 0 to 2 mm (3.88 vs 2.98 cm, respectively, P < .01). We also found that maximal ϵ and SR systolic and early diastolic values for the middle RV and apical IVS segments were significantly higher in patients with PR widths ≥ 3 mm ( Table 6 ). After adjustment for age and gender, the early diastolic values of SR were still significantly higher in patients with wider PR jet. NT-proBNP levels did not differ significantly in patients with wider PR compared with those with smaller PR.
